Niacin increases HDL biogenesis by enhancing DR4-dependent transcription of ABCA1 and lipidation of apolipoprotein A-I in HepG2 cells
| Autor: | Vaijinath S. Kamanna, Xi-Ming Xiong, Shobha H. Ganji, Moti L. Kashyap, Lin-Hua Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Transcription Genetic Apolipoprotein B human hepatoblstoma cell line Movement apolipoprotein A-I ATP binding cassette transporterA1 QD415-436 High-Density Lipoproteins Pre-beta Niacin Biochemistry chemistry.chemical_compound Endocrinology Internal medicine Gene expression ABCA1 Gene medicine polycyclic compounds direct repeat 4 Humans Phospholipids Research Articles Repetitive Sequences Nucleic Acid Regulation of gene expression biology Cholesterol Cholesterol HDL digestive oral and skin physiology HDL biogenesis Liver X receptor alpha food and beverages nutritional and metabolic diseases Biological Transport Hep G2 Cells Cell Biology Culture Media Gene Expression Regulation chemistry ABCA1 biology.protein ATP-Binding Cassette Transporters lipids (amino acids peptides and proteins) high density lipoproteins ATP Binding Cassette Transporter 1 |
| Zdroj: | Journal of Lipid Research, Vol 53, Iss 5, Pp 941-950 (2012) |
| ISSN: | 0022-2275 |
| Popis: | The lipidation of apoA-I in liver greatly influences HDL biogenesis and plasma HDL levels by stabilizing the secreted apoA-I. Niacin is the most effective lipid-regulating agent clinically available to raise HDL. This study was undertaken to identify regulatory mechanisms of niacin action in hepatic lipidation of apoA-I, a critical event involved in HDL biogenesis. In cultured human hepatocytes (HepG2), niacin increased: association of apoA-I with phospholipids and cholesterol by 46% and 23% respectively, formation of lipid-poor single apoA-I molecule-containing particles up to ∼ 2.4-fold, and pre β 1 and α migrating HDL particles. Niacin dose-dependently stimulated the cell efflux of phospholipid and cholesterol and increased transcription of ABCA1 gene and ABCA1 protein. Mutated DR4, a binding site for nuclear factor liver X receptor alpha (LXR α ) in the ABCA1 promoter, abolished niacin stimulatory effect. Further, knocking down LXR α or ABCA1 by RNA interference eliminated niacin-stimulated apoA-I lipidation. Niacin treatment did not change apoA-I gene expression. The present data indicate that niacin increases apoA-I lipidation by enhancing lipid efflux through a DR4-dependent transcription of ABCA1 gene in HepG2 cells. A stimulatory role of niacin in early hepatic formation of HDL particles suggests a new mechanism that contributes to niacin action to increase the stability of newly synthesized circulating HDL. |
| Databáze: | OpenAIRE |
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